Microporous membranes are well-known in the art. Such membranes have been used to ultrapurify water for use in making semiconductors, to filter paint compositions, to purify pharmaceuticals, and to perform a number of other widely divergent functions. Microporous membranes can have pore sizes ranging from about 0.01 to over 10 .mu.m; thus, they are suitable for removing particles of a variety of sizes.
Filters are typically used to remove suspended contaminants from fluids to provide for the passage of the clarified fluid (filtrate). A filter can achieve fluid clarification by different mechanisms. Suspended contaminants can be removed through mechanical sieving wherein particles larger than the pore rating of the filter medium are removed from the fluid. With this mechanism, filtration efficiency is essentially controlled by the size of the contaminant relative to the pore diameter of the filter medium.
Another mechanism by which a filter can achieve fluid clarification is through adsorption of suspended contaminants onto the filter surface. Removal of contaminants by this mechanism is controlled by the surface characteristics of the suspended contaminants and by the filter medium itself. Conventional filter media, however, adsorb many different particles without discretion. This often is undesirable in that many filtering applications require certain compounds to remain in the filtrate instead of adsorbing onto the surface of the filter medium. For example, in the filtering of pharmaceutical and biological compositions to remove contaminants, it is typically undesirable to remove preservatives, bacteriostats, and the like from the composition.
In the filtering of compositions, many different materials have been used to prepare filter media. Of particular usefulness have been polymers such as polyamides, polyesters, polyolefins, and the like. Many of the polymers which provide desirable structural characteristics, such as polyolefins, however, are hydrophobic and are not well-suited for filtering aqueous media at low fluid pressures. In order to render such filter media more suitable for aqueous filtration, techniques have been developed to render the surfaces of the filter media hydrophilic. For example, a polyvinylidene fluoride (PVDF) membrane, which is inherently hydrophobic, may be treated with a strong alkali solution in combination with an oxidizing agent to render it hydrophilic. It is believed, in this particular technique, that the base liberates hydrogen fluoride, and the oxidizing agent introduces a polar group onto the backbone of the PVDF, rendering the surface hydrophilic. This method has the disadvantage, however, of causing the filter medium to have a high affinity for positively charged preservatives, bacteriostats, and the like in fluids treated with the filter medium, thereby retaining such species rather then desirably passing them through with the filtrate.
Attempts at ameliorating such disadvantages have not met with success. For example, an excess number of positively charged quaternary ammonium compounds have been affixed by ionic bonds to a PVDF filter medium in order to reduce the affinity of positively charged preservatives, bacteriostats, and the like for the PVDF filter medium. This filter medium, however, has the drawback that the quaternary ammonium compounds are susceptible to leaching out, thereby rendering such a filter medium unsuitable in applications where the amount of extractables is to be kept to a minimum.
Other filter media have been disclosed as useful in the removal of bacterial endotoxins and heparin from blood. These filter media are comprised of a substrate matrix to which has been bonded quaternary ammonium compounds. The substrate matrix may be prepared from any suitable material, such as a polyamide, polyester, polyolefin, polysulfone, polyarylene oxide, polyarylene sulfide, and unsaturated nitriles. Many of these filter media, however, are not well-suited for applications in which one desires positively charged species such as preservatives, bacteriostats, and the like to pass through the filter medium and remain in the filtrate. For example, polyamides treated with quaternary ammonium compounds undesirably retain such positively charged species.
An important industrial use of microporous filter media is in the manufacture of pharmaceutical and biological compositions, such as ophthalmic solutions. Ophthalmic solutions for contact lenses and medicinal eye treatments typically contain a small amount (approx 0.01%) of preservatives such as benzalkonium chloride (BAK), quaternary ammonium compounds, and the like. During filtration, these preservatives adsorb onto the surface of a conventional filter medium to various extents, thereby decreasing the concentration of the preservatives in the filtrate to undesirable and/or unknown levels. Such adsorption represents a significant drawback to conventional filter media.
Thus, notwithstanding the wide variety of microporous filter media known in the art, there exists a need for a hydrophilic filter medium that is suitable for use in pharmaceutical and biological applications in which filtration of compositions is required to remove impurities such as bacteria while allowing for the passage of desirable positively charged species such as BAK along with the filtrate. The present invention provides such as a filter medium.
It is an object of the present invention to provide a microporous filter medium that is hydrophilic and is thus suitable for filtering aqueous media without the application of substantial pressure. It is another object of the present invention to provide a filter medium that has a positively charged surface with minimal susceptibility to the extraction of the agent that renders the membrane positively charged. It is a further object of the present invention to provide a filter medium that is suitable for filtering pharmaceutical and biological compositions such as ophthalmic solutions wherein desirable positively charged species such as BAK pass through the filter medium and are present in the filtrate.
These and other objects and advantages of the present invention, as well as additional inventive features, will be apparent from the description of the invention provided herein.